Isoquinoline, 1-chloro- → HCID 117661179, compound

HRID 588358Notes

Reaction equation

HRID 588358 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[NH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.CC([O-])(C)C.[K+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:2]1([NH:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 140539Isoquinoline, 1-chloro-HCID 634876Binap, (A+-)-HCID 1501974tert-butyl (3R)-3-aminopiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 117661179HCID 117661179, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 1-chloroisoquinoline (5.00 g, 30.6 mmol) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (7.34 g, 36.6 mmol) in anhydrous toluene (150 mL) was added t-BuOK (10.27 g, 91.7 mmol), BINAP (951 mg, 1.53 mmol), and Pd(OAc)2 (343 mg, 1.53 mmol). The reaction mixture was purged with nitrogen three times, and heated at 110° C. overnight. The reaction mixture was cooled to room temperature and poured into water. The mixture was then extracted with EtOAc (4×150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting dark solid was purified by silica gel column chromatography eluting with a gradient of (10-15%) EtOAc/petroleum ether to deliver the title compound (4.89 g, 49%) as a yellow solid.

Workup

  1. customThe reaction mixture was purged with nitrogen three times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionpoured into water
  4. extractionThe mixture was then extracted with EtOAc (4×150 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resulting dark solid was purified by silica gel column chromatography
  9. washeluting with a gradient of (10-15%) EtOAc/petroleum ether

Sources & evidence

ORD record
ord-dab3c2657a524955b057c7de9f553491
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

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